We are attempting to define the molecular basis of gene expression in higher organisms. Two model genetic systems, globin and immunoglobulin, are being used for this purpose. The work has involved recombinant DNA technology and has resulted in the cloning of several mouse globin and immunoglobulin genes whose nucleotide sequences now have been completely determined. These studies have permitted us to identify certain regions of the globin gene that are concerned with gene transcription and RNA splicing. We have also cloned the mouse globin genes in the simian virus SV40 and forced their accurate expression in infected cells, thus proving the universality of transcriptional and splicing mechanisms. In addition, the structural studies of the immunoglobulin genes indicate that immunoglobulin light chain gene diversity arises from hundreds of germline variable region genes that undergo recombination with one of five J- or joining segments adjacent to one germline constant region gene.